A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X + 2 + X] Horner–Wadsworth–Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed for a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner–Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process, followed by methylenation
